Targeted Therapies in Metastatic Colorectal Cancer: An Update

Bevacizumab is effective in combination with XELOX or FOLFOX-4

Background

Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that inhibits the vascular endothelial growth factor (VEGF), an angiogenesis factor secreted by tumour cells to bring about new blood vessel formation. Cancer Care Ontario guidelines recommend the addition of bevacizumab to improve overall survival as first-line therapy in patients with advanced colorectal cancer receiving 5-fluorouracil (5-FU)–based chemotherapy, and as second-line therapy for patients who did not receive bevacizumab as part of their initial treatment.2

The NO169663 trial was initially started as a randomized phase III study to compare the efficacy of XELOX (cape-citabine and oxaliplatin) versus FOLFOX-4 (5-fluorouracil, leucovorin, and oxaliplatin). The protocol was amended to include bevacizumab in a partially blinded 2 x 2 factorial design to determine the following objectives:

Study design

The study was a double-blind study with regard to bevacizumab and placebo administration (Table 1).

Patients with criteria such as ECOG PS ≤1, number of unidentified measurable lesions ≥1, no prior systemic therapy for advanced mCRC, and no prior treatment with oxaliplatin or bevacizumab were enrolled in the study. If patients had undergone prior adjuvant therapy, they should not have progressed during or within six months of completion.

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Contributors

Vera Hirsh, MD, FRCPCChief of the Hematology-Oncology Service, Santa Cabrini Hospital Associate Professor, Medicine and Oncology, McGill University
Associate Physician, Oncology Service, at the Royal Victoria, Montreal General, and Montreal Chest Hospitals
With a current practice in both hematology and oncology, Dr. Vera Hirsh is an associate professor of medicine and oncology at McGill University. Her research at the Quebec Pulmonary Unit focuses on the treatment of lung cancer, and she continues to chair ongoing international chemotherapy trials. Dr. Hirsh chaired the Quebec Lung Cancer Committee to establish guidelines for the treatment of lung cancer. In addition, she has published abstracts, articles, and book chapters. Dr. Hirsh is a member of advisory boards for many pharmaceutical companies and the Medical Oncology Standing Committee of RTOG.

Christine Cripps, MD, FRCPCMedical Oncologist, Director, Continuing Medical Education, Ottawa Hospital Regional Cancer Centre
Dr. Christine Cripps is a medical oncologist and director of the Continuing Medical Education Department at the Ottawa Hospital Regional Cancer Centre. She also holds a position of Associate Professor, Medicine at the University of Ottawa. A keen teacher, Dr. Cripps’ main areas of interest include gastrointestinal cancer and head and neck cancer. She also enjoys cycling, skiing, and sailing when time permits.

Stephen K. L. Chia, MD, FRCPCAssistant Professor of Medicine Department of Medicine University of British Columbia British Columbia Cancer Agency
Dr. Chia is a staff oncologist with the British Columbia Cancer Agency (BCCA), Vancouver, Canada. He also serves as physician coordinator for both the breast cancer and head and neck cancer clinical trials at the BCCA – Vancouver Cancer Centre. He is an active researcher in phase I-III trials in breast cancer, head and neck cancer and investigational new drugs. He is currently carrying out studies in breast cancer with grant funded research from the National Cancer Institute of Canada, Canadian Breast Cancer Alliance and Canadian Breast Cancer Foundation – British Columbia/Yukon Chapter. Dr. Chia is an active member of the British Columbia Breast Tumor Group, Breast Cancer Systemic Policy Group and Head and Neck Tumor Group.

José Chang, MD, FRCPCHead of Medical Oncology, RS McLaughlin Durham Regional Cancer Centre, Oshawa
Dr. José Chang is the principal investigator and site representative for the National Cancer Institute of Canada Clinical Trials Group, and is an examiner for the Medical Council of Canada. His research interests lie in the areas of breast cancer, melanoma, lymphoma, and quality of life during chemotherapy. Dr Chang has presented at major oncology meetings of the American Society of Clinical Oncology, San Antonio Breast Cancer Symposia, and European Breast Cancer Conference. A member of the editorial board of the journal Current Oncology, Dr. Chang has published in journals such as the Journal of Clinical Oncology, European Journal of Cancer, and Canadian Medical Association Journal.